Poor performance of students in chemistry shows that they are having difficulties in learning, mastering the content, and applying what they have learned in examinations. The purpose of this study was to find out the difference in (a) retention of information by students taught nuclear chemistry using the culturo-techno-contextual approach (CTCA) and lecture; (b) retention of information by male and female students taught nuclear chemistry using CTCA, and (c) the interaction effects of gender and method on retention of information by students taught nuclear chemistry using CTCA and lecture. Learning theories of Vygotsky's constructivism theory, Ausubel's theory of meaningful learning, and CTCA's philosophical framework were adopted. This study used explanatory sequential mixed methods; quasi-experimental research design was adopted. A total of 91 senior secondary II students (SS2) (equivalent of grade 11 in the American system) participated. Split-half was used to test the reliability of the nuclear chemistry achievement test (NCAT), and a Spearman--Brown of unequal length coefficient value of 0.80 was obtained. A statistically significant difference was found in the retention of information by students taught nuclear chemistry using CTCA and lecture [F(1,88) = 263.06; p = 0.00] which was in favor of the CTCA group (experimental). A statistically significant difference was not found for gender [F(1,46) = 0.39; p = 0.53]. The statistical interaction effect of method and gender was not significant [F(1,86) = 0.25; p = 0.62]. We recommended that the use of CTCA should be adopted by chemistry teachers in secondary schools to enhance learning.